Abstract Cadherin superfamily genes play a role in a wide variety of developmental processes and mature functions of the vertebrate brain. In the present study, we mapped in situ the expression ...pattern of five classic cadherins (Cdh4, Cdh6, Cdh7, Cdh8, Cdh11) and eight δ-protocadherins (Pcdh1, Pcdh7, Pcdh8, Pcdh9, Pcdh10, Pcdh11, Pcdh17 and Pcdh19) in the primary somatosensory cortex of the adult mouse. All of these cadherins show layer-specific expression profiles in primary somatosensory cortex. Some cadherins (for example, Cdh4, Cdh7, Pcdh8) mark subsets of cells within a given lamina, while other cadherins (Cdh11 and Pcdh10) are expressed more widely in multiple layers. Results from tyramide-based double-fluorescence in situ hybridization (FISH) provide evidence that most single neurons express more than one cadherin in a combinatorial fashion in all layers of cerebral cortex. This combinatorial code is rather comprehensive because pairwise expression of cadherins can assume any type of combination (complementarity, partial or complete overlap, subset-specific expression, cell-size specific expression, etc.). We propose that the combinatorial expression of multiple cadherin genes contributes to the molecular specification of the vast complexity of neurons in cerebral cortex.
delta-Protocadherins constitute a group of cadherins characterized by several conserved motifs in their cytoplasmic domains. We present a phylogenetic analysis that further divides this group into ...delta1-protocadherins (comprising protocadherin-1, -7, -9 and -11 or -X/Y) and delta2-protocadherins (comprising protocadherin-8, -10, -17, -18 and -19). The delta-protocadherin genes, which are located on different chromosomes in man and mouse, have a similar gene structure. They are expressed as multiple splice forms, differing mostly in their cytoplasmic domains. Some delta-protocadherins were reported to mediate weak cell-cell adhesion in vitro and cell sorting in vivo. In addition, individual delta-protocadherins might play important roles in signaling pathways, as they bind to proteins such as TAF1/Set, protein phosphatase-1alpha and the Frizzled 7 receptor. The spatiotemporally restricted expression of delta-protocadherins in different tissues and species and the results of their functional analysis, mainly in Xenopus, suggest that they play multiple, tightly regulated roles in vertebrate development.
Cadherins are superfamily of Ca2+-dependent transmembrane glycoproteins with more than 100 members. They play a role in a wide variety of developmental mechanisms, including cell proliferation, cell ...differentiation, cell–cell recognition, neurite outgrowth and synaptogenesis. We cloned 16 novel members of the classic cadherin and δ-protocadherin subgroups from ferret brain. Their expression patterns were investigated by in situ hybridization in the developing primary visual cortex (V1) of the ferret. Fifteen out of the 16 cadherins are expressed in a spatiotemporally restricted fashion throughout development. Each layer of V1 can be characterized by the combinatorial expression of a subset of cadherins at any given developmental stage. A few cadherins are expressed by subsets of neurons in specific layers or by neurons dispersed throughout all cortical layers. Generally, the expression of protocadherins is more widespread, whereas that of classic cadherins is more restricted to specific layers. At the V1/V2 boundary, changes in layer-specific cadherin expression are observed. In conclusion, our results suggest that cadherins provide a code of potentially adhesive cues for layer formation in ferret V1. The persistence of expression in the adult suggests a functional role also in the mature cortex.
Phylogenetic analysis of protocadherin genes identified a new gene subfamily, the delta-protocadherins, containing several conserved motifs in their cytoplasmic domains. This subfamily can be further ...subdivided into two subgroups, named delta1-protocadherins (comprising protocadherin-1, -7, -9, and -11 or X/Y) and delta2-protocadherins (comprising protocadherin-8, -10, -17, -18, and -19). The members of the delta1-protocadherin subgroup were analyzed in greater detail here. They share a similar gene structure that results in the expression of multiple alternative transcripts. All members of this subgroup have at least one transcript that contains a binding site for protein phosphatase-1alpha. Like most classic cadherins, each of three delta1-protocadherins analyzed in this study by in situ hybridization showed a unique expression pattern that differed from the patterns of the other delta1-protocadherins. Together, these results suggest that the members of the delta1-protocadherin subgroup exercise tightly regulated functions in the development, regionalization, and functional differentiation of the mouse brain.
Abstract ADAMs (a disintegrin and metalloprotease) are a family of trans-membrane multi-domain metalloproteases with multiple functions. So far, more than 35 ADAM family members have been identified ...from mammalian and nonmammalian sources. Although some functions of ADAMs have been elucidated, their expression patterns remain poorly investigated, especially during CNS development. Here, we cloned the open reading frames or full-length cDNAs of ADAM9, ADAM10, ADAM12, ADAM22 and ADAM23 from chicken embryonic brain, analyzed their evolutionary relationship, and mapped their expression in the embryonic chicken brain by in situ hybridization for the first time. In general, each of the five ADAMs shows a spatially restricted and temporally regulated expression profile. However, the types of tissues and cells, which express each of the five ADAMs, differ from each other. ADAM9 is predominantly expressed in the choroid plexus and in the ventricular layer. ADAM10 is expressed by developing blood vessels, oligodendrocytes, and subsets of neurons and brain nuclei. ADAM12 is expressed by very few brain nuclei, cerebellar Purkinje cells, restricted regions of the neuroepithelium, and some neurons in the deep tectal layers. ADAM22 expression is strong in some brain nuclei and in the pineal gland. ADAM23 is expressed by most gray matter regions and the choroid plexus. The differential expression patterns suggest that the five ADAMs play multiple and versatile roles during brain development.
The central nervous system (CNS) is divided into diverse embryological and functional compartments. The early embryonic CNS consists of a series of transverse subdivisions (neuromeres) and ...longitudinal domains. These embryonic subdivisions represent histogenetic fields in which neurons are born and aggregate in distinct cell groups (brain nuclei and layers). Different subsets of these aggregates become selectively connected by nerve fiber tracts and, finally, by synapses, thus forming the neural circuits of the functional systems in the CNS. Recent work has shown that 30 or more members of the cadherin family of morphoregulatory molecules are differentially expressed in the developing and mature brain at almost all stages of development. In a regionally specific fashion, most cadherins studied to date are expressed by the embryonic subdivisions of the early embryonic brain, by developing brain nuclei, cortical layers and regions, and by fiber tracts, neural circuits and synapses. Each cadherin shows a unique expression pattern that is distinct from that of other cadherins. Experimental evidence suggests that cadherins contribute to CNS regionalization, morphogenesis and fiber tract formation, possibly by conferring preferentially homotypic adhesiveness (or other types of interactions) between the diverse structural elements of the CNS. Cadherin-mediated adhesive specificity may thus provide a molecular code for early embryonic CNS regionalization as well as for the development and maintenance of functional structures in the CNS, from embryonic subdivisions to brain nuclei, cortical layers and neural circuits, down to the level of individual synapses.
We investigated the influence of Fourier power spectrum (1/f(p)) characteristics on face learning while recording ERPs that are associated with the representation of faces. Two image sets with an ...altered 1/f(p) characteristics were created. The first set consisted of stimuli with a STEEP SLOPE (1/f(3.5)) and therefore enhanced low spatial frequencies (LSF) and attenuated high spatial frequencies (HSF). The second set consisted of stimuli with a SHALLOW SLOPE (1/f(2)), similar to complex natural scenes and artwork, resulting in enhanced HSF and attenuated LSF. Faces with a SHALLOW SLOPE elicited larger N170 and N250 amplitudes and larger old/new effects for central positivity in comparison to unmodified faces. The opposite effect was observed for faces with a STEEP SLOPE that led to slower reaction times. This result suggests that diminishing the ratio of fine detail (HSF) to coarse structures (LSF) impairs face learning, whereas increasing it facilitates neurocognitive correlates of face learning.
During development, several genes that specify neuronal subtype identity are expressed in distinct dorsoventral domains of the spinal cord and hindbrain. Cadherin-7 (Cad7), a member of the cadherin ...family of adhesion molecules, is expressed by radial glia in a dorsal domain of the spinal cord basal plate in chicken. To study the regulation of the Cad7 gene, we ectopically expressed two known dorsoventral patterning genes, Shh and Pax7, in the caudal neural tube and in two brain regions at different stages of development by
in vivo electroporation. Results showed that Shh regulated the expression of Cad7 by radial glia in a concentration-dependent manner. Shh induced or repressed the expression of Cad7, at low and high concentrations, respectively. Furthermore, Pax7 inhibited the expression of Cad7. These results are compatible with a role of Shh and Pax7 in regulating endogenous Cad7 expression during spinal cord and hindbrain development. Our data show, for the first time, that Shh can regulate the expression not only of other gene regulatory factors, but also of Cad7, a morphoregulatory molecule that plays a role in axon elongation and neural circuit formation.
It is generally believed that the spinal cord and hindbrain consist of a motor basal plate and a sensory alar plate. We now have molecular markers for these territories. The relationship of migrating ...branchiomotor neurons to molecularly defined alar and basal domains was examined in the chicken embryo by mapping the expression of cadherin-7 and cadherin-6B, in comparison to genetic markers for ventrodorsal patterning (Otp, Pax6, Pax7, Nkx2.2, and Shh) and motoneuron subpopulations (Phox2b and Isl1). We show cadherin-7 is expressed in a complete radial domain occupying a lateral region of the hindbrain basal plate. The cadherin-7 domain abuts the medial border of Pax7 expression; this common limit defines, or at least approximates, the basal/alar boundary. The hindbrain branchiomotor neurons originate in the medial part of the basal plate, close to the floor plate. Their cadherin-7-positive axons grow into the alar plate and exit the hindbrain close to the corresponding afferent nerve root. The cadherin-7-positive neuronal cell bodies later translocate laterally, following this axonal trajectory, thereby passing through the cadherin-7-positive basal plate domain. Finally, the cell bodies traverse the molecularly defined basal/alar boundary and move into positions within the alar plate. After the migration has ended, the branchiomotor neurons switch expression from cadherin-7 to cadherin-6B.
These findings demonstrate that a specific subset of primary motor neurons, the branchiomotor neurons, migrate into the alar plate of the chicken embryo. Consequently, the century-old concept that all primary motor neurons come to reside in the basal plate should be revised.
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